tag:theconversation.com,2011:/au/topics/nerve-agent-5605/articlesNerve agent – The Conversation2017-04-11T01:52:07Ztag:theconversation.com,2011:article/759862017-04-11T01:52:07Z2017-04-11T01:52:07ZEnzymes versus nerve agents: Designing antidotes for chemical weapons<figure><img src="https://images.theconversation.com/files/164543/original/image-20170408-7394-159yw03.png?ixlib=rb-1.1.0&amp;rect=134%2C0%2C1547%2C871&amp;q=45&amp;auto=format&amp;w=496&amp;fit=clip" /><figcaption><span class="caption">Enzymes, the catalysts of biology, can engulf and break down hundreds of nerve agent molecules per second.</span> <span class="attribution"><span class="source">Image: Pymol. PDB 4E3T rcsb.org</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>A chemical weapons attack that killed <a href="http://www.bbc.com/news/world-middle-east-39500947">more than 80 people</a>, <a href="https://www.nytimes.com/2017/04/04/world/middleeast/syria-gas-attack.html">including children</a>, triggered the Trump administration’s <a href="https://www.nytimes.com/2017/04/07/world/middleeast/syria-attack-trump.html?_r=0">recent missile strikes</a> against the Syrian government. The use of illegal nerve agents – apparently by the Assad regime – violated <a href="https://ihl-databases.icrc.org/customary-ihl/eng/docs/v1_rul_rule74">international law</a>; President Trump said he was <a href="https://www.whitehouse.gov/the-press-office/2017/04/06/statement-president-trump-syria">moved to act by images</a> of the victims’ horrible deaths.</p>
<p>But there’s another path to mitigate the danger of chemical weapons. This route lies within the domains of science – the very same science that produced chemical weapons in the first place. Researchers in the U.S. and around the world, including here at the University of Washington’s <a href="http://www.ipd.uw.edu">Institute for Protein Design</a>, are developing the tools needed to quickly and safely destroy nerve agents – both in storage facilities and in the human body.</p>
<p>Nerve agents, a class of synthetic phosphorous-containing compounds, are <a href="https://doi.org/10.1093/jat/28.5.372">among the most toxic substances known</a>. Brief exposure to the most potent variants can lead to death within minutes. Once nerve agents enter the body, they irreversibly inhibit a vitally important enzyme called acetylcholinesterase. Its normal job within the nervous system is to help brain and muscle communicate. When a nerve agent shuts down this enzyme, classes of neurons throughout the central and peripheral nervous systems quickly get overstimulated, leading to <a href="https://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/nerve-agents/#c4118">profuse sweating, convulsions and an excruciating death by asphyxiation</a>.</p>
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<a href="https://images.theconversation.com/files/164556/original/image-20170408-29390-75dm34.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/164556/original/image-20170408-29390-75dm34.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip"></a>
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<span class="caption">U.S. Marine Corps specialists performing decontamination procedures.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:U.S._Marine_Corps_chemical,_biological,_radiological_and_nuclear_(CBRN)_defense_specialists_with_Marine_Wing_Headquarters_Squadron_(MWHS)_3,_3rd_Marine_Aircraft_Wing,_perform_decontamination_procedures_during_130430-M-EF955-271.jpg">Sgt. Keonaona Paulo</a></span>
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<p>Chemical weapons are often associated with wars of the previous century – mustard gas in WWI, Zyklon B in WWII. But the worst variety, nerve agents, were <a href="http://cen.acs.org/articles/94/i41/Nazi-origins-deadly-nerve-gases.html">never deployed in the world wars</a>, though Nazi scientists developed the first generation of these compounds. Gerhard Schrader, the so-called <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2008.00972.x/full">father of nerve agents</a>, didn’t begin life as a Nazi scientist – he was developing new pesticides to combat world hunger when he accidentally synthesized the first organophosphorus nerve agent. Later, he led the research team that produced sarin, or GB, the most toxic of the all the so-called G-series nerve agents. The U.S. government stated with <a href="https://www.whitehouse.gov/the-press-office/2017/04/06/press-briefing-secretary-state-rex-tillerson-and-national-security">“very high confidence” that sarin was used</a> in the recent attack near Idlib, Syria.</p>
<p>Beginning in 2013, teams from the Organization for the Prohibition of Chemical Weapons went to Syria and, with help from the Danish, Norwegian, Russian, Chinese and <a href="https://www.defense.gov/News/Article/Article/602835">U.S. government</a>, <a href="https://www.opcw.org/news/article/destruction-of-syrian-chemical-weapons-completed/">destroyed all declared stockpiles</a> of Syrian chemical weapons. It seems that either not all of Assad’s stockpiles were in fact <a href="https://www.nytimes.com/2017/04/07/world/middleeast/werent-syrias-chemical-weapons-destroyed-its-complicated.html?_r=0">declared and destroyed, or that new nerve agents arrived</a> in Syria – either via the black market or chemical synthesis – in the intervening years. </p>
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<a href="https://images.theconversation.com/files/164553/original/image-20170408-7394-1opyv30.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/164553/original/image-20170408-7394-1opyv30.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip"></a>
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<span class="caption">Empty sarin containers at Pine Bluff Arsenal.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Empty_sarin_containers_at_Pine_Bluff_Arsenal.jpg">U.S. Army</a></span>
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<h2>Clearing chemical weapons</h2>
<p>Twenty-first-century chemists, biochemists and computer scientists are working right now to sap chemical weapons of their horrifying power by designing counter agents that safely and efficiently destroy them. </p>
<p>Sarin sitting in a container – as opposed to in a human body – is relatively easy to destroy. The simplest method is to add a soluble base and heat the mixture to near-boiling temperatures. After several hours, the vast majority – more than 99.9 percent – of the deadly compound can be broken apart by a process called hydrolysis. This is how <a href="https://www.hdiac.org/node/1936">trained specialists</a> dispose of chemical weapons like sarin. </p>
<p>Nerve agents that make their way inside the body are a different story. For starters, you clearly cannot add a near-boiling base to a person. And because nerve agents kill so quickly, any treatment that takes hours to work is a nonstarter.</p>
<p>There are chemical interventions for warding off death after exposure to certain chemical weapons. Unfortunately, these interventions are costly, difficult to dose properly and <a href="https://doi.org/10.1111/j.1742-7843.2011.00678.x">are themselves quite toxic</a>. The chemical antidotes pralidoxime and the cheaper atropine <a href="http://www.chicagotribune.com/news/opinion/editorials/ct-syria-gas-attack-assad-sarin-chlorine-edit-0405-jm-20170404-story.html">were deployed</a> after recent attacks in Syria, but <a href="http://time.com/4727073/idlib-chemical-attack-sarin-gas-pralidoxime/">doctors in the area worry</a> their dwindling supplies offer little protection against possible future attacks. </p>
<p>For a medical intervention to work after nerve gas exposure, it has to work fast. If a first responder administers a sarin-destroying molecule, each therapeutic molecule must be capable of breaking down through hydrolysis <a href="https://dx.doi.org/10.3109/10242429709003196">hundreds of nerve agent molecules per second</a>, one after another. </p>
<p>Enzymes, the genetically encoded catalysts of biology, are up for such a task. Famous enzymes include lactase, which breaks down milk sugars in those who are lactose tolerant. Another known as RuBisCO is vital to the process of carbon fixation in plants. The most efficient enzymes in your body can perform <a href="http://www.vivo.colostate.edu/hbooks/molecules/carbonic_anhydrase.html">a million reactions per second</a>, and do so under chemically mild conditions. </p>
<p>Aside from their astonishing speed, enzymes often display an equally impressive selectivity. That is, they react with only a small number of structurally similar compounds and leave all other compounds alone. Selectivity is useful in the context of the chemical soup that is the cell but problematic when it comes to xenobiotics: those compounds which are foreign to one’s biology. Man-made organophosphates such as sarin are xenobiotics. There are no enzymes that hydrolyze them well – or so we thought.</p>
<p>When farmers spray pesticides, much of it ends up on the ground. Soil bacteria living nearby are challenged by high doses of these potent foreign chemicals. It turns out that <a href="https://doi.org/10.1111/j.1752-4571.2010.00175.x">efficient detoxifying enzymes have recently evolved</a> inside some of these microbes as a result.</p>
<p>Scientists have identified and isolated a small number of these enzymes and tested them on a range of nasty compounds, including nerve agents, which are structurally similar to some pesticides. A select few did indeed show hydrolytic activity.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/164558/original/image-20170408-29399-hwdml4.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/164558/original/image-20170408-29399-hwdml4.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip"></a>
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<span class="caption">Scientists are using computers to design a new generation of proteins to solve 21st-century problems.</span>
<span class="attribution"><span class="source">UW Institute for Protein Design</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<h2>Improving on the discovery</h2>
<p>Researchers have taken these naturally occurring enzymes as raw material. Then, using <a href="http://pubs.acs.org/doi/abs/10.1021/cb4004892">computer modeling and controlled evolution in the lab</a>, we’ve bolstered the efficiency of the originally found anti-nerve agent enzymes. Enzymes that initially showed only modest activity have been turned into potential therapeutics against VX – a chemical cousin of sarin and the most toxic nerve agent of all.</p>
<p>In a proof-of-concept study conducted jointly by researchers in Germany and Israel in late 2014, guinea pigs under anesthesia were exposed to lethal doses of VX, followed by optimized VX-destroying proteins. Low doses of the protein drug, even after a 15-minute delay, resulted in <a href="https://doi.org/10.1016/j.toxlet.2014.09.003">survival of all animals</a> and only moderate toxicity.</p>
<p>Despite these promising advances, no enzyme yet exists which is efficient enough for lifesaving use in people. Scientists are <a href="https://doi.org/10.1038/nchembio.777">refining these microscopic machines</a>, and <a href="https://doi.org/10.1038/nature19946">new paradigms in computer-aided protein engineering</a> are unlocking the door to this and other applications of biomolecular design. We may be only a few years away from developing the kind of therapeutics that would make chemical weapons a worry of the past. </p>
<p>As the world grieves over the latest attacks in Syria, it is worth keeping in mind the awesome and often complex power of science. In trying to combat hunger, one might accidentally invent liquid death. In studying soil microbes, one might discover a tool to prevent atrocities.</p><img src="https://counter.theconversation.com/content/75986/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Haydon works at the Institute for Protein Design and receives funding from the National Science Foundation.</span></em></p>Scientists invented chemical weapons; some are now working to destroy them. New biomolecular design techniques let researchers design proteins that can destroy nerve agents in bodies.Ian Haydon, Doctoral Student in Biochemistry, University of WashingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/736032017-02-24T07:08:24Z2017-02-24T07:08:24ZExplainer: what is VX nerve agent and how does it work?<figure><img src="https://images.theconversation.com/files/158248/original/image-20170224-32705-vb4fpp.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=496&amp;fit=clip" /><figcaption><span class="caption">Little protection against the deadly VX nerve agent.</span> <span class="attribution"><span class="source">Shutterstock/Bubbers BB</span></span></figcaption></figure><p>The substance that could be responsible for the death Kim Jong-nam, the half-brother of the North Korean leader Kim Jong-un, was the VX nerve agent, <a href="https://www.theguardian.com/world/2017/feb/24/kim-jong-nam-north-korea-killed-chemical-weapon-nerve-agent-mass-destruction-malaysian-police">according to preliminary reports</a> from Malaysian police.</p>
<p>Kim Jong-nam died on February 13 from a seizure on his way to hospital after complaining that a woman had sprayed chemicals on his face at Kuala Lumpur airport.</p>
<p>The Royal Malaysia Police <a href="http://www.rmp.gov.my/news-detail/2017/02/24/media-statement-inspector-general-of-police">said in a statement</a> that the results of dry swab tests on the “death of a North Korean national” identified the chemical as “Ethyl S-2-Diisopropylaminoethyl Methylphosphonothiolate”, also known as “VX nerve agent”.</p>
<h2>What is VX?</h2>
<p>VX is a lethal chemical weapon in the V-series of nerve agents. Although commonly referred to as nerve gases, the chemicals are usually liquids at room temperature.</p>
<p>The V-series were first developed in the UK in the mid-1950s. Like all <a href="https://theconversation.com/chemical-weapons-in-syria-who-what-where-when-why-17581">nerve agents</a>, the V-series block the biological action of the enzyme <a href="https://www.merriam-webster.com/dictionary/acetylcholinesterase">acetylcholinesterase</a> (AChE). </p>
<p>AChE is responsible for metabolising the neurotransmitter acetylcholine, which in turn is responsible for the transmission of a nerve impulse across the gap (called a <a href="https://www.youtube.com/watch?v=WhowH0kb7n0">synapse</a>) between two nerve cells.</p>
<p>By preventing AChE from metabolising acetylcholine, the nerve agent causes the synapse to become flooded with the neurotransmitter. This saturation leads to the nerve being constantly switched “on”. <a href="https://www.youtube.com/watch?v=uJTdx1GbEqU">In the case of nerves that control muscles</a>, this means that the muscle is constantly receiving a signal to contract. </p>
<p>Constant muscle contraction becomes a problem when the muscles in question are the ones that control the expansion of the rib cage, to fill the lungs with air. If these muscles are continuously trying to contract, the body is constantly trying to fill the lungs with air, and thus not allowing the body to expel air from the lungs. </p>
<p>The victim of such a nerve agent usually dies from <a href="https://www.youtube.com/watch?v=_oouhWBdYf0">asphyxiation</a> due to not being able to breathe out.</p>
<h2>Other symptoms</h2>
<p>Although asphyxiation is usually the ultimate cause of death, exposure to AChE inhibitors has a wide range of symptoms, including runny nose, drooling and contraction of the pupils.</p>
<p>Unlike the nerve agent sarin, which was used to attack the <a href="http://www.japantimes.co.jp/news/2015/03/20/national/tokyo-marks-20th-anniversary-of-aums-deadly-sarin-attack-on-subway-system/">Tokyo subway</a> and <a href="http://www.un.org/zh/focus/northafrica/cwinvestigation.pdf">Ghouta</a>, a suburb of Damascus in Syria, the V-series are termed “persistent” agents.</p>
<p>In chemical weapons terms, persistent means that the agent has a <a href="https://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/nerve-agents/#c4121">low volatility</a>. In turn, this means that it can be used in relatively confined spaces (such as an airport terminal) with less risk of obvious adverse effects on bystanders or the perpetrators.</p>
<p>But low doses of nerve agent have been linked with <a href="https://www.ncbi.nlm.nih.gov/pubmed/16962140">long-term effects</a> in people who did not exhibit clinical symptoms at the time of exposure.</p>
<p>All nerve agents can affect the body either through inhalation or skin contact. The V-series are usually associated with entering the body through skin contact.</p>
<p>Another advantage of using VX for any would-be assassin, is that the amount of VX needed to kill is around 10mg (1/100th of a gram). That is around a tenth of the amount of sarin needed to cause death, and a droplet around the size of the nib of a ballpoint pen. </p>
<h2>Who has VX?</h2>
<p>VX has been used before as a mode of assassination. Members of <a href="http://www.japantimes.co.jp/news/2015/03/14/national/history/cult-attraction-aum-shinrikyos-power-persuasion/#.WK_UlhL5hVo">Aum Shinrikyo</a> used VX to <a href="http://www.japantimes.co.jp/news/2003/04/25/national/cases-asahara-stands-accused-in/#.WK_UJRLfpVo">kill a suspected traitor</a> to the Japanese cult. </p>
<p>The cult also provided their members with the antidote to nerve agent poisoning during the attack on the Tokyo subway. This shows that it is possible for perpetrators to use a nerve agent as a weapon in close proximity, without needing to use bulky protective equipment, or risk lethal exposure themselves.</p>
<p>Since discovery, V-agents have been researched, produced and stockpiled by several countries. Most of those countries have now given up their offensive chemical weapons programs and are in the process of destroying their stockpiles and placing their means of production under international monitoring via the <a href="https://www.opcw.org/">Organisation for the Prohibition of Chemical Weapons (OPCW)</a>.</p>
<p>OPCW oversees the <a href="https://www.opcw.org/chemical-weapons-convention/download-the-cwc/">Chemical Weapons Convention</a> (CWC). Under the CWC, <a href="https://www.opcw.org/chemical-weapons-convention/annexes/annex-on-chemicals/schedule-1/">VX and all nerve agents (and their precursors that have no other legitimate industrial use)</a> are illegal to produce or procure.</p>
<p>North Korea is one of only four countries that have not signed or acceded to the CWC. The North Korean government is <a href="http://www.nti.org/learn/countries/north-korea/chemical/">believed to have a stockpile of chemical weapons</a>, including V-series agents and can manufacture them in industrial quantities.</p><img src="https://counter.theconversation.com/content/73603/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martin Boland does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond the academic appointment above.</span></em></p>Malaysian police have identified a chemical the could have led to the death of the North Korean leader's half brother as the deadly VX nerve agent.Martin Boland, Senior Lecturer of Medicinal and Pharmaceutical Chemistry, Charles Darwin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/175812013-08-28T04:43:31Z2013-08-28T04:43:31ZChemical weapons in Syria: who, what, where, when, why? <figure><img src="https://images.theconversation.com/files/30081/original/msyxn8qj-1377660066.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=496&amp;fit=clip" /><figcaption><span class="caption">UN inspectors will face several problems determining what has happened in Damascus.</span> <span class="attribution"><span class="source">EPA/STR</span></span></figcaption></figure><p>It’s been a little more than a week since <a href="http://www.washingtonpost.com/world/national-security/un-to-inspect-alleged-chemical-weapons-attack-in-syria-lawmakers-call-for-us-military-response/2013/08/25/e171162e-0d94-11e3-bdf6-e4fc677d94a1_story.html">reports surfaced</a> of a large-scale chemical weapon attack in Syria. Governments in Europe and the <a href="http://www.reuters.com/article/2013/08/26/us-syria-crisis-usa-kerry-idUSBRE97P0RJ20130826">United States</a> have accused the Syrian government of attacking their own people, while the Assad government has <a href="http://www.aljazeera.com/news/middleeast/2013/08/20138271141631363.html">pointed the finger</a> at its opponents. </p>
<p>The United Nations currently has <a href="http://www.huffingtonpost.com/2013/08/27/syria-chemical-weapons_n_3820586.html">inspectors in Damascus</a>, who have been tasked with finding out if chemical weapons were used and, if so, by whom.</p>
<p>It’s not a simple matter to decide if a chemical attack has occurred. The inspectors will be looking for evidence to support or refute one of several possibilities:</p>
<ul>
<li>a non chemical cause, such as <a href="http://en.wikipedia.org/wiki/Mass_hysteria">mass hysteria</a></li>
<li>a chemical cause not related to chemical weapons</li>
<li>an attack using chemical weapons, but an improvised delivery system</li>
<li>a military chemical weapons attack using artillery or bombs.</li>
</ul>
<p>In media interviews, former weapons inspectors have said that the symptoms are in line with <a href="http://www.theguardian.com/world/2013/aug/22/syria-deaths-strike-sarin-alleged-chemical">a nerve agent such as sarin</a> rather than the effects of a blistering agents such as <a href="http://www.bt.cdc.gov/agent/sulfurmustard/basics/facts.asp">sulphur mustard</a>.</p>
<p>Looking at video purported to be from the site (see below), there is none of the usual blistering associated with mustard gas attacks, although that is not always immediate, while the combination of contracted pupils, uncontrolled mucus from nose/mouth and ataxia (uncoordinated movements) would suggest nerve agent or similar poisoning.</p>
<figure>
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<figcaption><span class="caption">WARNING: this video contains graphic images.</span></figcaption>
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<h2>What are nerve agents and how do they work?</h2>
<p>Nerve agents are <a href="http://medical-dictionary.thefreedictionary.com/organophosphorus+compound">organophosphorus compounds</a> that interfere with the transmission of nerve signals. Nerve signals are how the brain receives information and sends commands to the body. Signals are electrical impulses that travel along cells such as those in the spinal cord. When the signal reaches the end of one cell it must cross a gap, called <a href="http://psychology.about.com/od/sindex/f/what-is-a-synapse.htm">a synapse</a>, to reach the next nerve cell.</p>
<p>The signal is transmitted across the synapse by chemicals called neurotransmitters. These are released from the end of a nerve cell, travel across the synapse and bind to a protein switch on the beginning of the next nerve cell, which in turn generates a new electrical impulse. </p>
<p>The transmission process does not destroy the neurotransmitter. Instead, the neurotransmitter will remain in the synapse, binding to the switch over and over again until it is either destroyed or removed from the synapse.</p>
<p>One neurotransmitter, <a href="http://neuroscience.uth.tmc.edu/s1/chapter11.html">acetylcholine</a>, is destroyed by an enzyme called <a href="http://www.ncbi.nlm.nih.gov/gene/43">acetylcholine esterase</a>. Nerve agents bind to and block the action of acetylcholine esterase. Without the enzyme’s action, the amount of acetylcholine in the synapse never decreases. </p>
<p>Large amounts of acetylcholine repeatedly activate the protein switch leading to a constant stream of nerve signals.</p>
<p>If the nerve is one leading to a muscle, the continuous nerve signals prevent the muscle from relaxing. In fact, the muscle is continuously activating (contracting). When this occurs in the muscles that control breathing, they can only breathe in (the diaphragm contracts when we breathe in). As the victim cannot breathe out they asphyxiate. </p>
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<a href="https://images.theconversation.com/files/30080/original/gw96tj5w-1377659758.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/30080/original/gw96tj5w-1377659758.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip"></a>
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<span class="caption">A photo made from a handout video released by the Syrian opposition Moadamiyeh media centre is said to show UN inspectors collecting samples from a victim who was allegedly affected by a chemical gas weapon, in Moadamiyeh suburb, Damascus, Syria, on August 26. EPA cannot provide confirmation of content, authenticity, place, date and source.</span>
<span class="attribution"><span class="source">Moadamiyeh Media Center/EPA </span></span>
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<p>Causing victim’s nerves to constantly signal to contract muscles leads to the symptomatic contraction of the pupils and “twitching” seen in cases of nerve-agent poisoning. In practice, this effect is usually seen in the later stages of poisoning, earlier symptoms being a runny nose and confusion.</p>
<p>There are several nerve agents that have differing physical and chemical properties. Some have the consistency of motor oil, while others will readily evaporate at room temperature. All are lethal in very small doses. A few tenths of a gram will kill an average man. Lethal exposure can be via ingestion (eating/drinking), skin contact with the liquid or by breathing in the agent as a gas.</p>
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<span class="caption">Sulphur mustard’s molecular structure.</span>
<span class="attribution"><span class="source">Wikimedia Commons</span></span>
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<h2>Determining the presence of nerve agents</h2>
<p>The UN inspectors will face several problems determining what happened in Damascus. Nerve agents are unstable in the normal environment and will break down readily. The breakdown products are non-toxic and not particularly notable in the environment of an industrial civilisation. This means it will be very difficult, if not impossible, to detect the use of nerve agents in the air or in substances on the street.</p>
<p>All known military nerve agents are organophosphorus compounds to the extent that certain groups of phosphorus compounds are outlawed for production and storage by the 1993 [chemical weapons convention](http://www.opcw.org/chemical-weapons-convention/annex-on-chemicals/b-schedules-of-chemicals/schedule-1/](http://www.opcw.org/chemical-weapons-convention/annex-on-chemicals/b-schedules-of-chemicals/schedule-1/ ) (which came into force in 1997, but Syria is not a signatory). </p>
<p>Many of the materials that are necessary, known as precursors, for production of the lethal compounds are similarly outlawed. But some precursors are themselves <a href="http://www.opcw.org/chemical-weapons-convention/annex-on-chemicals/b-schedules-of-chemicals/schedule-3/">useful industrial chemicals</a>, with uses in agriculture and chemical processes.</p>
<p>It is unlikely that the inspectors will find residual nerve agent in the environment. The more volatile agents would have blown away with the wind within hours of the incident. Compounds such as sarin break down <a href="http://hazmap.nlm.nih.gov/category-details?id=1452&amp;table=copytblagents">within one and two</a> days in the open.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/30082/original/t8rx46yf-1377660385.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip">
<figcaption>
<span class="caption">On August 26, UN weapons experts set out from Damascus to Eastern Ghouta, the area on the outskirts of the Syrian capital, where chemical weapons were allegedly used and over which West has warned of consequences for the regime of President Bashar al-Assad. The opposition said the August 21 bombardment by government forces using a poisonous gas left 1,300 people dead. The government has vehemently denied the claim.</span>
<span class="attribution"><span class="source">STR/EPA</span></span>
</figcaption>
</figure>
<p>Similarly, the compounds are metabolised in the body. A blood sample taken from someone several days after receiving a non-lethal dose will probably not contain any nerve agent. It is also important to remember that the toxic dose is minute compared with the mass of the body. Samples taken a day after the <a href="http://en.wikipedia.org/wiki/Sarin_gas_attack_on_the_Tokyo_subway">Tokyo subway sarin attack</a> contained ~100ng/mL (approximately 1 part in 10 million).</p>
<p>Instead of looking for the agent itself, the inspectors test for a <a href="http://www.news-medical.net/health/Metabolites-What-are-Metabolites.aspx">metabolite</a> (breakdown product) of the compound. The metabolites that will be sought are specific and can be used to identify exposure a particular compound. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/30083/original/txxxmt2w-1377661139.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip"><img alt="" src="https://images.theconversation.com/files/30083/original/txxxmt2w-1377661139.jpg?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=237&amp;fit=clip"></a>
<figcaption>
<span class="caption">The molecular structure of sarin.</span>
<span class="attribution"><span class="source">Wikimedia Commons</span></span>
</figcaption>
</figure>
<p>This would be achieved by taking urine or blood samples from victims and sending those to a laboratory equipped with appropriate gas or liquid <a href="http://www.chemicool.com/definition/chromatography.html">chromatographs</a> (equipment which separates mixtures) connected to sensitive <a href="http://hyperphysics.phy-astr.gsu.edu/hbase/magnetic/maspec.html">mass spectrometers</a>.</p>
<p>It is also possible to detect the nerve agent bound to the acetylcholine esterase. This method is similar to that for detecting metabolites. It potentially could be used up to two months after an attack. But each of these methods relies on a sufficiently high dose being received by the victim, which clearly suggests that they would be killed by the effects of the nerve agent and may have since been buried.</p>
<p>Other physical evidence the inspectors will look for will include expended shell or bomb casings that could have contained chemical weapons. They will also study the pattern of injury and death that the incident left on the ground. Release of a compound from containers at ground level will have a different dispersion from artillery bursting in the air.</p>
<p>If the UN inspectors can get sufficient blood and/or urine samples from victims, they should be able to determine the cause of the incident. </p>
<p>But if a chemical weapon attack is confirmed, it may be somewhat harder to positively identify the perpetrators.</p><img src="https://counter.theconversation.com/content/17581/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martin Boland does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>It’s been a little more than a week since reports surfaced of a large-scale chemical weapon attack in Syria. Governments in Europe and the United States have accused the Syrian government of attacking…Martin Boland, Research Fellow, University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/138812013-05-21T04:55:52Z2013-05-21T04:55:52ZExplainer: what are chemical weapons?<figure><img src="https://images.theconversation.com/files/24093/original/6r3c9drm-1368997143.jpg?ixlib=rb-1.1.0&amp;rect=0%2C0%2C2784%2C1796&amp;q=45&amp;auto=format&amp;w=496&amp;fit=clip" /><figcaption><span class="caption">Hopefully this will remain a rare sight.</span> <span class="attribution"><span class="source">Edgaras Zvirblys</span></span></figcaption></figure><p>There was chaos on the streets of Halajba in March 1988. In this corner of Iraq, at the time Iraqi Kurdistan, people had suddenly started experiencing cold-like symptoms – tight chest and nasal congestion. Within a few minutes, those effects morphed into feeling dizzy and sick. Many started vomiting and some lost control of their bladders and bowels. Finally there were severe convulsions, as muscles that control breathing were paralysed, before succumbing to death.</p>
<p>The cause for this gruesome event was sarin, a nerve agent that is classed as a chemical weapon. <a href="http://news.bbc.co.uk/onthisday/hi/dates/stories/march/16/newsid_4304000/4304853.stm">This incident in Iraq</a> killed thousands and was the last confirmed mass use of chemical weapons. But if <a href="http://www.bbc.co.uk/news/world-middle-east-22557347">new reports</a> are proved right, the most recent use of chemical weapons may have happened as recently as last month. It is believed that the Syrian government, which in July 2012 confirmed that they possess chemical weapons, may have used nerve gas to fight the rebels.</p>
<h2>Weapons of mass destruction</h2>
<p>Defining a chemical weapon is not simple, because many chemicals with legitimate uses, such as insecticides, could also be used for sinister purposes. This is why the Organisation for the Prohibition of Chemical Weapons (OPCW) <a href="http://www.opcw.org/about-chemical-weapons/what-is-a-chemical-weapon/">defines</a> them as: </p>
<blockquote>
<p>All toxic chemicals and their precursors, except when used for purposes permitted by the Chemical Weapons Convention, are chemical weapons. </p>
</blockquote>
<p>By toxic chemical they mean “any chemical which through its chemical action can cause death, temporary incapacitation or permanent harm to humans or animals”. The OPCW <a href="http://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/">categorises chemical weapons</a> on how they work:</p>
<p></p><li><strong>Blister agents</strong> act via inhalation or contact with the skin. As the name suggests they can cause horrific chemical burns leading to blisters. They also cause blindness and permanent damage to the lungs. The class includes mustard gases used in the trenches of World War I and during the Iran-Iraq conflict of the 1980s.<p></p>
<p></p></li><li><strong>Nerve agents</strong> such as sarin are highly toxic and work rapidly by affecting the way that nerve signals are transmitted through the body to the brain. Sarin, for instance, acts by attaching itself to a protein that is 400 times its own size and disrupts nerve-to-nerve communication. This makes the victim lose control of all its bodily functions.<p></p>
<p></p></li><li><strong>Blood agents</strong> interfere with the way that blood cells use and transport oxygen. Examples include cyanide, which may well have seen <a href="http://books.google.co.uk/books?id=PbwyF5Kj8YkC&amp;pg=PA28&amp;lpg=PA28&amp;dq=british+crimean+war+cyanide&amp;source=bl&amp;ots=-FtIcEWCDm&amp;sig=wcv1TIJW3TVuAfUKMT8HTZKx6T8&amp;hl=en&amp;sa=X&amp;ei=v0CZUer7AoPGPZbdgZgH&amp;ved=0CDgQ6AEwAQ#v=onepage&amp;q=british%20crimean%20war%20cyanide&amp;f=false">its first use</a> in warfare during the British Crimean war, and arsenic.<p></p>
<p></p></li><li><strong>Choking agents</strong> affect the victims’ ability to breath and also have corrosive affects on the skin and eyes. Chlorine gas, used in World War II, is an example of a choking agent.<p></p>
<p></p></li><li><strong>Non-lethal chemical weapons</strong>, a final category by OPCW, includes riot control agents such as tear gas.<p></p>
<h2>Your morning coffee could kill you</h2>
<p>Scientists define the toxicity of a chemical by something called an LD50, which is the dose of that chemical required to kill half a test population. The unit of measurement for LD50 is grams per kilogram of weight of an animal. It is usually experimentally recorded by subjecting rats or mice with the chemical. </p>
<p>While LD50 is useful to understand the toxicity of chemical weapons, it can be applied to any chemical. Here is a list of chemicals, in the ascending order of their toxicities:
</p><ul>
<li>Sugar 29.7g/kg
</li><li>Salt 3g/kg
</li><li>Paracetamol 1.9g/kg
</li><li>Arsenic 0.76g/kg
</li><li>Caffeine 0.192g/kg
</li><li>Mustard gas 0.1g/kg
</li><li>Nicotine 0.05g/kg
</li><li>Cyanide 0.0064g/kg
</li><li>Sarin 0.00017g/kg
</li><li>Botulinum toxin 0.000000001g/kg
</li></ul>
<p> You may have rightly guessed then that the contents of your morning coffee could be more toxic than arsenic, if you so wished. Similarly botox, which is short for botulinum toxin, is regularly injected in people’s foreheads as a beauty treatment. This just shows that it is the way chemicals are used that turns them into weapons, not necessarily what’s in them.</p><p></p></li><img src="https://counter.theconversation.com/content/13881/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Lorch does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>There was chaos on the streets of Halajba in March 1988. In this corner of Iraq, at the time Iraqi Kurdistan, people had suddenly started experiencing cold-like symptoms – tight chest and nasal congestion…Mark Lorch, Senior Lecturer in Biological Chemistry, University of HullLicensed as Creative Commons – attribution, no derivatives.